Objective(s): The purpose of this study was to conduct a meta-analysis on human microRNAs (miRNAs) expression data of endometriosis tissue profiles versus those of normal controls and to identify novel putative diagnostic markers. Materials andMethods: PubMed, Embase, Web of Science, Ovid Medline were used to search for endometriosis miRNA expression profiling studies of endometriosis. The miRNAs expression data were extracted, and study quality of each article was assessed. The frequently reported miRNAs with consistent regulation were screened out by a meta-profiling algorithm. The putative targets of consistently expressed miRNAs were predicted by using four target prediction tools (TargetScan, PicTar, miRanda, miRDB), and gene ontology pathway enrichment analysis (KEGG and Panther pathways) of the miRNA targets were carried out with GeneCodis web tool. Results: A total of 194 related literatures were retrieved in four databases. One hundred and thirty four differentially expressed miRNAs were found in the 12 microRNA expression profiling studies that compared endometriosis tissues with normal tissues, with 28 miRNAs reported in at least two studies, and 9882 candidate genes retrieved for 13 consistently expressed miRNAs. Kyoto encyclopedia of genes and genomes (KEGG) and Panther pathways enrichment analysis showed that endometriosis related differently expressed miRNA targets were mainly enriched in cancer, endocytosis, Wnt signalling pathway, and angiogenesis. It showed that these differently expressed miRNAs and gene are potential biomarkers of endometriosis. Conclusion: miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic agent in endometriosis.

Metabolic syndrome (MetS) as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases.

Objective(s): Atherosclerosis is an important risk factor for coronary heart disease. Neuropeptide Y (NPY) and its receptors, located in peripheral tissue such as white adipose tissue, have been linked to obesity and fat storage. The role of NPY in atherosclerosis has not yet been fully studied, so this study was conducted to further investigate the effect of BIIE 0246, an NPY receptor antagonist, on aortic intima-media thickness and size and number of adipocyte cells in normal and obese mice. Materials and Methods: Tests were performed on 24 male C57BL/6 mice. The animals were divided into four groups as follows: control (normal), obese (high-fat diet), normal+NPY receptor antagonist (1 μM, 100 µl/Kg BIIE0246 intraperitoneally) and obese+NPY receptor antagonist (n=6 each). After 14 days, the animals were sacrificed and epididymal adipose tissue and thoracic aorta were removed. Evaluations were made for adipocyte cell number and size and for aortic intima-media thickness. Results: The group on a high-fat diet showed a significantly decreased number of adipocyte cells and increased cell size (P<0.05). BIIE0246 application changed the cell number of adipocyte in normal mice (P=0.05); however, it did not change adipocyte cell size and aortic intima-media thickness in obese and normal mice (P>0.05). Conclusion: NPY receptor antagonist had no effect on adipocyte cell size and aortic intima-media thickness; however, it decreased cell number in the normal group indicating likely involvement in the progression of obesity

Objective(s): Due to unsatisfactory response or intolerable side effects of current drugs, treatment of essential tremor remains inadequate. Thus, we aimed to investigate the protective and therapeutic effects of aqueous and ethanolic extracts of Crocus sativus (saffron), and its active consistent, safranal, on the harmaline-induced tremor in mice. Materials and Methods: To induce tremor, harmaline (30 mg/kg) was injected intraperitoneally. Test groups were also given the aqueous and ethanolic extracts of saffron (40, 80, and 160 mg/kg) as well as safranal (0.1, 0.3, and 0.5 ml/kg), intraperitoneally, 10 min before harmaline administration (prophylactic study) or 10 min after the onset of tremors (curative study). The latency of onset, duration, and intensity of tremor were recorded. Results: The extracts (80 and160 mg/kg) dose dependently attenuated duration of harmaline-induced tremors as did reference drug, propranolol (2 and 5 mg/kg). Only the highest dose of extracts (160 mg/kg) attenuated intensity of harmaline-induced tremors throughout the study. Safranal at the doses of (0.1 and 0.3 ml/kg) but not 0.5 ml/kg attenuated duration and intensity of tremor. Onset of tremor increased with the extracts (80 and 160 mg/kg) in prophylactic study, as the effect observed with propranolol at the dose of 5 mg/kg. Safranal did not affect the latency of tremor. Conclusion: Both aqueous and ethanolic extracts of saffron and with a less effect, low doses of safranal, have relatively protective and suppressive effects on the harmaline-induced tremor and different constituents of extracts seem to participate in the protective effects against harmaline induced tremor.

Objective(s): Lipocalin2 (Lcn2) gene is highly expressed in response to various types of cellular stresses. The precise role of Lcn2 has not been fully understood yet. However, it plays a key role in controlling vital cellular processes such as proliferation, apoptosis and metabolism. Recently it was shown that Lcn2 decreases senescence and increases proliferation of mesenchymal stem cells (MSC) with finite life span under either normal or oxidative stress conditions. However, Lcn2 effects on immortal cell line with infinite proliferation are not defined completely. Materials and Material and Methods: HEK-293 cells were transfected with recombinant pcDNA3.1 containing Lcn2 fragment (pcDNA3.1-Lcn2). Expression of lipocalin2 in transfected cells was evaluated by RT-PCR, real time RT-PCR, and ELISA. Different cell groups were treated with H2O2 and WST-1 assay was performed to determine their proliferation rate. Senescence was studied by β-galactosidase and gimsa staining methods as well as evaluation of the expression of senescence-related genes by real time RT-PCR. Results: Lcn2 increased cell proliferation under normal culture condition, while the proliferation slightly decreased under oxidative stress. This decrease was further found to be attributed to senescence. Conclusion: Our findings indicated that under harmful conditions, Lcn2 gene is responsible for the regulation of cell survival through senescence.

Objective(s): FOXP3 gene is an X-linked gene that encodes FOXP3 protein, an essential transcription factor in CD4+CD25+FOXP3+ regulatory T (Treg) cells. We aimed, in the present study, to investigate the association of two FOXP3 polymorphisms, -2383 C/T (rs3761549) and IVS9+459 T/C (rs2280883), with lung cancer. Materials and Methods: In a case-control study we analyzed genotypes and alleles frequencies at -2383 C/T and IVS9+459 T/C positions in 156 patients with lung cancer and 156 age and sex matched healthy controls in Southern Iranian population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The data were verified by direct automated DNA sequencing. Results: The frequency of -2383 T allele was significantly higher in the patients than in the control group (11.8% versus 5.9%, P-value=0.04, OR=2.13, 95%CI=1.04-4.54). T allele frequency at IVS9+459 T/C position was higher, compared to the controls, in the patients who presented the disease over 55 years old (69.9% versus 59.1%, P-value=0.04, OR=1.61, 95%CI=1.01-2.55) and also in SCLC patients (77.8% versus 59.1%, P-value=0.03, OR=2.42, 95%CI=1.05-5.59). No significant differences were found in the genotypes and haplotypes distributions between the cases and controls. A high degree of linkage disequilibrium was observed between two polymorphisms. Conclusion: As the first study dealing with -2383 C/T and IVS9+459 T/C in lung cancer, our data conclusively suggest the association of -2383 T allele with susceptibility to lung cancer in Iranian population. The association of IVS9+459 T allele with susceptibility to lung cancer in old patients suggests the age-dependent effects of FOXP3 gene on cancer occurrence.

Objective(s):Multidrug resistance (MDR) of cancer cells is a major obstacle to successful chemotherapy. Overexpression of breast cancer resistance protein (BCRP) is one of the major causes of MDR. In addition, it has been shown that PI3K/Akt signaling pathway involves in drug resistance. Therefore, we evaluated the effects of novel approaches including siRNA directed against BCRP and targeted therapy against PI3K/Akt signaling pathway using LY294002 (LY) to re-sensitize breast cancer MCF7 cell line to mitoxantrone (MTX) chemotherapy. Materials and Methods: Anticancer effects of MTX, siRNA, and LY alone and in combination were evaluated in MCF7 cells using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: MTT and apoptosis assays showed that both MTX and LY inhibited cell proliferation and induced apoptosis in MCF7 cells. Results indicated that inhibition of BCRP by siRNA or PI3K/Akt signaling pathway by LY significantly increased sensitivity of MCF7 cells to antiproliferation and apoptosis induction of MTX. Furthermore, MTX showed G2/M arrest, whereas LY induced G0/G1 arrest in cell cycle distribution of MCF7 cells. Combination of siRNA or LY with MTX chemotherapy significantly increased accumulation of MCF7 cells in the G2/M phase of cell cycle. Conclusion: Combination of MTX chemotherapy with BCRP siRNA and PI3K/Akt inhibition can overcome MDR in breast cancer cells. This study furthermore suggests that novel therapeutic approaches are needed to enhance anticancer effects of available drugs in breast cancer

Objective(s):Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. One of the hallmarks of AD is an abnormal accumulation of fibril forms of tau protein which is known as a microtubule associated protein. In this regard, inhibition of tau aggregation has been documented to be a potent therapeutic approach in AD and tauopathies. Unfortunately, the available synthetic drugs have modest beneficial efficacy with several side effects. Therefore, pipeline drugs from natural sources with anti-aggregation properties can be useful in the prevention and treatment of AD. Among medicinal plants, saffron (Crocus sativus, L.), as a traditional herbal medicine has different pharmacological properties and can be used as treatment for several nervous system impairment including depression and dementia. Crocin as a major constituent of saffron is the glycosylated form of crocetin. Materials and Methods: In this study, we investigated the inhibitory effect of crocin on aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods and cell culture. Results: Results revealed that tau protein under the fibrillation condition and in the presence of crocin had enough stability with low tendency for aggregation. Crocin inhibited tau aggregation with IC50 of 100 µg/ml. Furthermore, transmission electron microscopy images confirmed that crocin could suppress the formation of tau protein filaments. Conclusion: Inhibitory effect of crocin could be related to its interference with nucleation phase that led to increases in monomer species of tau protein. Based on our results, crocin is recommended as a proper candidate to be used in AD treatment.

Objective(s): The present study aims to study the alteration of glutamatergic transmission in the dorsal horn neurons and the effect of gabapentin on oxaliplatin-induced neuropathic pain in rats. Materials and Methods: Oxaliplatin (5 mg/kg) or saline was administered to adult male Sprague-Dawley rats. Gabapentin (60 mg/kg, IP) or vehicle was injected daily. Mechanical allodynia was assessed using a series of von Frey filaments. The expression of glutamate receptor subunits (NR2B and GluR1) and brain-derived neurotrophic factor (BDNF) was measured in the dorsal horn. The glutamatergic strength was recorded in the spinal cord slices. Results: Administration of oxaliplatin induced significant hyperreactivity to mechanical stimuli in rats, which was attenuated by gabapentin. Significant increase in the expression of BDNF was found in the dorsal horn in rats receiving oxaliplatin, which was prevented by gabapentin. Further studies also observed a significant increase in the expression of GluR1 and NR2B, as well as enhanced glutamatergic transmission in the dorsal horn neurons in rats treated with oxaliplatin. The upregulation of glutamatergic transmission was significantly reversed by gabapentin. Conclusion: These results illustrated an increased expression of BDNF and enhanced glutamatergic transmission in rats with oxaliplatin-induced neuropathic pain, which was markedly attenuated by gabapentin.

Objective(s):Brucellosis is a well-known domestic animal infectious disease, which is caused by Brucella bacterium. GroEL antigen increases Brucella survival and is one of the major antigens that stimulates the immune system. Hence, the objective of the present study was cloning and bioinformatics analysis of GroEL gene. Materials and Methods: The full-length open reading frame of this gene was amplified by specific primers and cloned into pTZ57R/T vector. Also, the sequence of this gene in the Brucella melitensis strain Rev 1 was submitted to the NCBI gene bank for the first time. Several prediction software applications were also used to predict B and T-cell epitopes, secondary and tertiary structures, antigenicity ability and enzymatic degradation sites. The used software applications validated experimental results. Results: The results of phylogenetic analysis showed that the GroEL sequence had near homology with other species instead of other Brucella spp. The bioinformatics tools used in the current study were validated by the results of four different experimental epitope predictions. Bioinformatics analysis identified eight B and seven T-cell epitopes. Conclusion: According to the antigenic ability and proteasomal cleavage sites, four (150-160, 270-285,351-361 and 385-395) common epitopes were predicted for GroEL gene. Bioinformatics analysis showed that these regions had proper epitope characterization and so may be useful for stimulation of cell-mediated and humoral immunity system.

Objective(s):Tumor-associated antigen (TAA) subunit-based vaccines constitute promising tools for anticancer immunotherapy. However, a major limitation in the development of such vaccines is the poor immunogenicity of peptides when used alone.The aim of this study was to develop an efficient vaccine delivery system and adjuvant to enhance anti-tumor activity of a synthetic HER2/neu derived peptide (P5). Materials and Methods: P5 peptide was encapsulated with different liposomal formulations composed of DMPC:DMPG:Chol:DOPE and loaded with monophosphoryl lipid A (MPL). All formulations were characterized for their physicochemical properties. To evaluate vaccine efficacy, BALB/c mice were first immunized with free peptide or liposomal formulations, then, inoculated with a subcutaneous injection of TUBO tumor cells. Enzyme-linked immunospot, cytotoxicity and intracellular cytokine assays, as well as tumor size and animal survival analysis, were performed to evaluate the immune responses. Results: The results demonstrated that P5 encapsulated into liposomal formulations was not able to induce CD8 and CD4 T cells to produce IFN-γ. That is why, a potent CTL response and antitumor immunity was not induced. Conclusion: The Lip-DOPE-P5-MPL formulation in spite of using pH-sensitive lipid to direct intracellular trafficking of peptide to MHC I presentation pathway and MPL to enhance peptide adjuvanticity was interesting. The failure in inducing anti-tumor immunity may be attributed to low uptake of anionic conventional liposomes by dendritic cells (DCs) that have negative surface charge.

Objective(s):Atherosclerosis is chronic inflammatory process triggered by oxidative stress. Oxidative stress can increase hydrogen peroxide (H2O2)level, which induce atherosclerosis through the processes such as formation of perivascular adipose tissue (PVAT), foam cells, and atherosclerotic plaque. Antioxidant is needed to control negative effects of oxidative stress. One source of antioxidant, which has potential to be developed, is PsP from Ganoderma lucidum. This study aims to prove the effect of PsP in decreasing H2O2, PVAT, foam cells and atherosclerotic plaque. Materials and Methods: This study was experimental randomized post-test with control group design using 25 Rattus norvegicus Wistar strain rats. Rats were divided into 5 groups (negative control, positive control, and 3 high-fat diet group with PsP dose: 50, 150, 300 mg/kgBW). Measured parameters were H2O2, PVAT, foam cell, and atherosclerotic plaques. Analysis of variance (ANOVA) was used for statistical analysis, followed by post hoc test. Results: Mean H2O2 levels, PVAT thickness, foam cell numbers, and atherosclerotic plaque were low in negative control group. ANOVA showed that PsP significantly (P<0.05) reduced H2O2 levels, PVAT thickness, foam cells numbers and atherosclerotic plaque width. Conclusion: PsP dose of 300 mg/kgBW has the most significant effect in decreasing H2O2 levels, PVAT thickness, number of foam cells, and atherosclerotic plaque width. Based on the results of this research, PsP can be recommended as antioxidant to control pathogenesis of atherosclerosis.

Objective(s): Intracerebral injection of bone marrow stromal cells (BMSCs) is being investigated as a therapeutic tool to prevent Alzheimer's disease (AD). Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. Materials and Methods: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. Results: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. Conclusion: Our results showed that BMSCs intratechal administration could be a promising method for treatment ofAlzheimer’s disease in rat model.

Resistin (RETN), recently found to be relevant to inflammation and inflammatory disorders. We, therefore, aimed to investigate the potential role of RETN gene polymorphism in pathogenesis of acne vulgaris with familial history. We investigated the RETN-420C/G polymorphism in 180 patients with acne vulgaris and 180 healthy individuals in a case-control association analysis. In this study, we also investigated the heritability of the RETN susceptible allele from 140 trio families with acne affected offspring. The genotyping was performed by polymerase chain reaction and direct DNA sequencing.The RETN-420C/G polymorphism was significantly associated with acne in patients compared with healthy controls (P=0.014). The minor allele G at -420 was more prevalent in cases vs. controls (P=0.002). The RETN-420C/G polymorphism was significantly associated with severity of acne vulgaris in patients (P=0.0097). The results of a transmission disequilibrium test revealed a significant association between the RETN-420C/G polymorphism and acne vulgaris (P<0.001). For the first time in the literature, to our knowledge, we demonstrate a significant association of the RETN-420C/G functional polymorphism with familial acne vulgaris.